The Zivkovic Lab was recently awarded a grant from the California Department of Public Health Alzheimer’s Disease Research Program to study the changes in HDL particles and exosomes across stages of dementia. The one-year project will support research using cutting edge technologies to discover how “liquid biopsies” can reveal disease processes related to lipid metabolism in the brain. The Zivkovic lab will collaborate with Dr. John Olichney, Professor in the Department of Neurology, and Clinical Core Director of the UC Davis Alzheimer’s Disease Center, and Dr. Carlito Lebrilla, Distinguished Professor in the Department of Chemistry to carry out this work.
Dr. Zivkovic recently became part of the second phase of the NIH Common Fund funded Extracellular RNA Communications Consortium 2 (ERCC2). As site PI of this cooperative agreement Dr. Zivkovic is also working with UC Davis colleague Dr. Carlito Lebrilla and a team of collaborators including the project PI Dr. Ken Witwer, Associate Professor of Molecular and Comparative Pathobiology at Johns Hopkins University, Wyatt Vreeland at the National Institute of Standards and Technology (NIST), and Juan Pablo Tosar at the Faculty of Science in Uruguay.
The concept of a “liquid biopsy” is that molecules in easily-accessed biological fluids such as blood can tell us about processes occurring in less easily-accessed tissue compartments, such as the brain. Liquid biopsies are an exciting new strategy for biomarker discovery and for the development of therapies. Extracellular RNA (exRNA) is a particularly attractive molecular component of liquid biopsy because RNA species can be specifically amplified, and certain short RNAs (sRNAs) such as microRNAs (miRNAs) are highly stable because of small size and association with protective binding proteins. exRNA are transported in blood in distinct RNA carriers including extracellular vesicles (e.g. exosomes), lipoprotein particles (e.g. HDL and LDL), and free ribonucleoproteins.
In this ERCC2 project, Drs. Zivkovic and Lebrilla are working with the rest of the team to develop novel methodologies to isolate and characterize the three main subclasses of exRNA carrier particles. The team is incorporating advanced technologies for particle isolation including size exclusion chromatography and asymmetrical flow field flow fractionation, and for characterizing the particle characteristics and contents including dynamic light scattering and liquid chromatography mass spectrometry.